Many reactions in living organisms are caused by entrance of extracellular information into cells and by propagation of the information in the cells. Membrane receptors serve as mediators through which extracellular information is transmitted into cells. Among them, GPCRs having seven transmembrane domains is well known as a major category of membrane receptors.
When a ligand (such as amino acids, peptides or amines) binds to a GPCR, the GPCR transmits its information into a cell via a trimeric G protein. G proteins coupled to GPCRs are classified into Gs, Gi, Gq, and the like, which activate/inactivate different effector pathways (e.g., cAMP pathway, cGMP pathway, and phospholipase C pathway), respectively. For example, α1-adrenergic receptor is mainly coupled to Gq protein to promote phospholipase C system, which produces diacylglycerol and inositol trisphosphate, thus increasing intracellular Ca2+. α2-adrenergic receptor is mainly coupled to Gi protein to suppress adenylate cyclase system, thus decreasing cAMP. Further, β-adrenergic receptor is mainly coupled to Gs protein to promote adenylate cyclase system, which thus increases cAMP.
GPCRs widely occur and function in our body. For example, α1-adrenergic receptors exist peripherally in blood vessel, prostate, and produce the contractions. Further, α1-adrenergic receptors are known to function in central nervous system. β-adrenergic receptors in heart and fat tissue play important roles in heart rate and lipolysis.
GPCRs and their signal transduction systems are known not only to control the physiological homeostasis in our body but also to be involved in pathophysiological status of various diseases. Therefore, in order to treat the diseases it will be very significant to identify the GPCRs which are related to the diseases and then to develop their specific drugs (such as agonists or antagonists).
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